title: IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes.
abstract: To identify proinflammatory cytokine responsive genes in the myocardium, we used differential display to study RNA isolated from neonatal rat cardiac myocytes treated with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Sequence analysis of differential display products confirmed by reverse Northern blots revealed one clone as the partial sequence of an Eph-related receptor tyrosine kinase (r-EphA3). In cardiac myocytes, 36-h exposure to TNF-alpha and IL-1 beta reduced r-EphA3 transcripts to 59.9% (P < 0.01) of control levels; this effect was largely dependent on IL-1 beta. Western blot analysis showed that changes in r-EphA3 protein levels reflect that seen for transcripts. Cardiac nonmyocytes expressed substantially lower levels of r-EphA3. Full-length r-EphA3 cDNA clone (3,077 base pair) yielded an amino acid sequence with 90-98% homology to the Eph receptor human EphA3, chick EphA3, and mouse EphA3. In the adult rat, r-EphA3 transcripts were most abundant in the heart, brain, and lung. These results suggest that IL-1 beta may exert its effect on cardiac myocytes at least in part by altering r-EphA3 expression.
authors.affiliation: Cardiovascular Research Laboratories, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.forename: C F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: A M
authors.initials: AM
authors.lastname: Feldman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology; D002478:Cells, Cultured; D002645:Chickens; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000737:chemistry; D036121:Receptor, EphA3; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C491718:EPHA3 protein, human; C491717:Epha3 protein, mouse; C110404:Epha3 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3